title: Comparison of transesophageal echocardiographic analysis and circulating biomarker expression profile in calcific aortic valve disease.
abstract: OBJECTIVE
  Aortic valve sclerosis (AVSc), the early asymptomatic stage of calcific aortic valve disease (CAVD), is characterized by a progressive thickening of the aortic cusps without obstruction of the left ventricular outflow. In spite of its high prevalence, there are no molecular markers to characterize the early stages of CAVD before it progresses to a severe, symptomatic stage of aortic valve stenosis (AVS). The study aim was to identify any correlation between circulating biomarkers and transesophageal echocardiography (TEE) evaluation.
  
  
  METHODS
  A total of 330 patients with various degrees of CAVD was enrolled into the study. Blood was collected from each patient prior to surgery, and analyzed using ELISA kits following the manufacturers' instructions.
  
  
  RESULTS
  Significantly higher plasma osteopontin (OPN) levels were observed in AVSc patients (72.7 +/- 1.8 ng/ml; p < 0.001) and AVS patients (64.3 +/- 5.1 ng/ml; p < 0.001) when compared to controls (30.3 +/- 1.8 ng/ml). Parathyroid hormone (PTH) levels in AVSc and AVS patients (164.1 +/- 16.5 and 134.3 +/- 14.6 pg/ml; p < 0.001 and p = 0.04, respectively) were also significantly higher than in controls (61.8 +/- 4.92 pg/ml). Upon further analysis, plasma levels of OPN (p < 0.001) and PTH (p < 0.001) were found to be significantly higher in asymptomatic AVSc patients, even before calcium deposition was detected on TEE evaluation. Fetuin-A levels were lower at all stages of CAVD when compared to controls (p < 0.001 and p < or = 0.05, respectively), but were comparable among the patient groups. NT-proBNP levels were significantly higher in AVS patients than in controls (p < or = 0.01).
  
  
  CONCLUSIONS
  Serum levels of OPN, PTH, and fetuin-A showed a significant association with different stages of CAVD, with variations in their levels occurring before calcium nodules are visualized during TEE evaluation. The study results may help not only to provide a better understanding of the progression of CAVD but also to develop new tools that can be used to stage these patients.
authors.affiliation: Perelman School of Medicine, University of Pennsylvania, Department of Surgery, Division of Cardiovascular Surgery, Philadelphia, PA 19036, USA.
authors.forename: Rachana
authors.initials: R
authors.lastname: Sainger
authors.forename: Juan B
authors.initials: JB
authors.lastname: Grau
authors.forename: Emanuela
authors.initials: E
authors.lastname: Branchetti
authors.forename: Paolo
authors.initials: P
authors.lastname: Poggio
authors.forename: Eric
authors.initials: E
authors.lastname: Lai
authors.forename: Erblina
authors.initials: E
authors.lastname: Koka
authors.forename: William J
authors.initials: WJ
authors.lastname: Vernick
authors.forename: Robert C
authors.initials: RC
authors.lastname: Gorman
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Bavaria
authors.forename: Giovanni
authors.initials: G
authors.lastname: Ferrari
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001021:Aortic Valve / Q000000981:diagnostic imaging / Q000473:pathology*; D001024:Aortic Valve Stenosis / Q000097:blood* / Q000000981:diagnostic imaging; D001120:Arginine / Q000031:analogs & derivatives / Q000097:blood; D015415:Biomarkers / Q000097:blood*; D002114:Calcinosis / Q000097:blood* / Q000000981:diagnostic imaging; D016022:Case-Control Studies; D017548:Echocardiography, Transesophageal; D005260:Female; D006801:Humans; D008297:Male; D020097:Natriuretic Peptide, Brain / Q000097:blood; D053495:Osteopontin / Q000097:blood; D010281:Parathyroid Hormone / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D012598:Sclerosis; D012720:Severity of Illness Index; D060749:alpha-2-HS-Glycoprotein / Q000378:metabolism
chemical_list: C556354:AHSG protein, human; D015415:Biomarkers; D010281:Parathyroid Hormone; D010446:Peptide Fragments; D060749:alpha-2-HS-Glycoprotein; C109794:pro-brain natriuretic peptide (1-76); D053495:Osteopontin; D020097:Natriuretic Peptide, Brain; C018524:N,N-dimethylarginine; D001120:Arginine